(71f) Biocatalysis in Microorganisms and Applications of Phytochemical Analogs

Flavonoids are a diverse group of secondary metabolites found ubiquitously in the plant kingdom. Their associated health benefits have gained an increasing amount of attention towards for use as medicinal agents, supplements and natural colorants but a growing number of unnatural flavonoids are currently being investigated as therapeutic agents. In fact, the majority of recently approved pharmaceuticals are natural products themselves or are structurally related to them. Our group has been focusing on utilizing metabolic engineering to synthesize natural and unnatural plant flavonoids (isoflavones, flavanones, flavones, dihydroflavonols, stilbenes, flavonols, catechins and anthocyanins) in microorganisms and their applications. Our progress has covered the reconstruction of the plant biosynthetic pathway within both Escherichia coli and Saccharomyces cerevisiae. We have been able to increase flavonoid production yields by a variety of methods including expression of recombinant enzymes, inhibiting competing pathways or through gene knockouts. Using these engineered platforms, we have explored the synthesis of novel flavonoid analogs using a mutasynthesis approach. Studies conducted in our lab have shown that these compounds have significant biological activity towards estrogen receptors, digestive enzyme inhibition and antimicrobial properties. The variety of novel compounds produced has given us insights to both the biosynthetic reaction mechanisms and structure-function analysis of inhibitory properties against therapeutic targets.